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Functional implications of the heterogeneity of the lipid second messenger-metabolizing enzyme, diacylglycerol kinase, in neurons

Research Project

Project/Area Number 14380351
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Nerve anatomy/Neuropathology
Research InstitutionYamagata University

Principal Investigator

GOTO Kaoru  Yamagata University, School of Midicine, Deparment of Anatomy and Cell Biology, Professor, 医学部, 教授 (30234975)

Co-Investigator(Kenkyū-buntansha) WAKABAYASHI Ichiro  Yamagata University, School of Midicine, Deparment of Anatomy and Cell Biology, Professor, 医学部, 教授 (70220829)
SAINO Sachiko  Yamagata University, School of Midicine, Deparment of Anatomy and Cell Biology, Associate Professor, 医学部, 講師 (50312559)
HOZUMI Yasukazu  Yamagata University, School of Midicine, Deparment of Anatomy and Cell Biology, Assistant Professor, 医学部, 助手 (00372334)
NAKANO Tomoyuki  Yamagata University, School of Midicine, Deparment of Anatomy and Cell Biology, Assistant Professor, 医学部, 助手 (00333948)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥12,500,000 (Direct Cost: ¥12,500,000)
Fiscal Year 2004: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2003: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥6,500,000 (Direct Cost: ¥6,500,000)
Keywordsphospholipid / diacylglycerol / diacylglycerol kinase / neuron / nucleus / signal transduction / second messenger / シナプス / 細胞内局在 / 核細胞質移行
Research Abstract

We have so far isolated and characterized several isozymes of diacylglycerol kinase(DGK) from rat brain cDNA library. Our series of studies revealed the heterogeneity of the enzyme in terms of molecular structure, tissue distribution, enzymatic activity, and the localization of gene expression, and provided functional implications for DGK family. Interestingly, most of the isozymes show abundant expression in distinct patterns in the brain, suggesting the importance of this enzyme in neuronal function. Among these, mRNA for DGKbeta is detected uniquely in restricted regions of the brain, such as the caudate-putamen, accumbens nucleus, olfactory tubercle, olfactory bulb, and hippocampal pyramidal cell layer. In our previous experiments using transfected COS-7 cells, DGKbeta is shown to be distributed throughout the cytoplasm in a filamentous pattern. However, detailed subcellular localization of this isozyme remains unclear in neurons. To address this point, we performed in the present … More study immunohistochemical examination on rat brain with a specific antibody against DGKbeta, together with cDNA-transfection into primary cultured neurons using GFP expression vector. Under the con focal laser scanning microscopy, the immunoreactivity for DGKbeta was detected in neurons of the corresponding brain regions that express the mRNA abundantly and appeared as ring-like structures. To examine the presice localization of DGKbeta, we employed immunoelectron microscopy to localize the immunolabelled structures. Dark immunoreaction products in pre-embedding immunoperoxidase electron microscopy were distributed diffuselly within dendrites and spines in neurons. Furthermore, most of the particulate metal marker in pre-embedding silver-intensified immunogold electron microscopy were deposited in association with the cytoplasmic face of the cell membrane in dendrites and spines in neurons. In the transfected hippocampal neurons in culture, GFP-DGKbeta was predominantly detected as button-like structures in the presumed dendritic processes. These results suggest that DGKbeta may be involved in synaptic transmission at postsynaptic site and signal transduction in neuronal cells.
In addition, it should be also noted that two of the isozymes, DGKzeta and DGKiota, contain a nuclear localization signal, suggesting possible roles of these isozymes in nuclear processes. We have revealed selective translocation of DGKzeta in hippocampal neurons under transient forebrain ischemia. We found that DGKzeta is translocated from the nucleus to the perikaryal cytoplasm in hippocampal pyramidal cells immediately after 20 min of ischemic insult. Previous studies have shown that neuronal death in the hippocampus occurs after 48-72 h reperfusion, but not immediately, under transient ischemia, a phenomenon called "delayed neuronal death." Therefore we speculate that the nucleo-cytoplasmic translocation of DGKzeta in the hippocampal neurons at an early phase of ischemic insult may be one of the triggering events of the delayed neuronal death, but not a result of dying process. Less

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (37 results)

All 2005 2004 2003 Other

All Journal Article (31 results) Publications (6 results)

  • [Journal Article] Cardiac-specific overexpression of diacylglycerol kinase zeta prevents Gq protein-coupled receptor agonist-induced cardiac hypertrophy in transgenic mice.2005

    • Author(s)
      Arimoto et al.
    • Journal Title

      Circulation (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Diacylglycerol kinase and animal models : the pathophysiological roles in the brain and heart2005

    • Author(s)
      Goto et al.
    • Journal Title

      Advance Enzyme Regul. (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Differential Regulation of Diacylglycerol Kinase Isozymes in Cardiac Hypertrophy.2005

    • Author(s)
      Yahagi et al.
    • Journal Title

      Biochem. Biophys. Res. Comm. 332

      Pages: 101-108

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Gene Expression, CeUular localization and Enzymatic Activity of Diacylglycerol Kinase Isozymes in Rat Ovary and Placenta.2005

    • Author(s)
      Toya et al.
    • Journal Title

      Cell Tissue Res 320

      Pages: 525-33

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression and localization of diaylglycerol kinase isozymes and enzymatic features in rat lung.2005

    • Author(s)
      Katagiri et al.
    • Journal Title

      Am. J. Physiol. Lung Cell Mol. Physiol. 288

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Ade no virus- me diate d overexpression of diacylglycerol kinase-zeta inhibits, endothelin-1-induced cardiomyocyte hypertrophy.2005

    • Author(s)
      Takahashi et al.
    • Journal Title

      Circulation 111

      Pages: 1510-6

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cardiac-specific overexpression of diacylglycerol kinase zeta prevents Gq protein-coupled receptor agonist-induced cardiac hypertrophy in transgenic mice.2005

    • Author(s)
      Arimoto T, Takeishi Y, Takahashi H, Shishido T, Niizeki T, Koyama Y, Shiga R, Nozaki N, Nakajima O, Nishimaru K, Abe J, Endo M, Walsh RA, Goto K, Kubota I.
    • Journal Title

      Circulation (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Diacylglycerol kinase and animal models : the pathophysiological roles in the brain and heart.2005

    • Author(s)
      Goto K, Nakano T, Hozumi Y.
    • Journal Title

      Advance Enzyme Regul. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Differential Regulation of Diacylglycerol Kinase Isozymes in Cardiac Hypertrophy.2005

    • Author(s)
      Yahagi H, Takeda M, Asaumi Y, Okumura K, Takahashi R, Takahashi J, Ohta J, Tada H, Minatoya Y, Sakuma M, Watanabe J, Goto K, Shirato K, Kagaya Y.
    • Journal Title

      Biochem.Biophys.Res.Comm. 332

      Pages: 101-108

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Gene Expression, Cellular localization and Enzymatic Activity of Diacylglycerol Kinase Isozymes in Rat Ovary and Placenta.2005

    • Author(s)
      Toya M, Hozumi Y, ItoT, TakedaM, Sakane F, Kanoh H, SaitoH, Hiroi M, Kurachi H, Kondo H, Goto K.
    • Journal Title

      Cell Tissue Res. 320

      Pages: 525-533

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression and localization of diaylglycerol kinase isozymes and enzymatic features in rat lung.2005

    • Author(s)
      Katagiri Y, Ito T, Saino-Saito S, Hozumi Y, SuwabeA, Otake K, Sata M, Kondo H, Sakane F, KanohH, Kubotal, Goto K.
    • Journal Title

      Am.J.Physiol.Lung Cell Mol.Physiol. 288

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Adenovirus-mediated overexpression of diacylglycerol kinase-zeta inhibits endothelin-1-induced cardiomyocyte hypertrophy2005

    • Author(s)
      Takahashi H, Takeishi Y, Seidler T, Arimoto T, Akiyama H, Hozumi Y, Koyama Y, Shishido T, Tsunoda Y, Niizeki T, Nozaki N, Abe J, Hasenfuss G, Goto K, Kubota I.
    • Journal Title

      Circulation 111

      Pages: 1510-1516

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression and localization of diacylglycerol kinase isozymes and enzymatic features in rat lung2005

    • Author(s)
      Katagiri et al.
    • Journal Title

      Am J Physiol Lung Cell Mol Physiol (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Gene Expression, Cellular localization and Enzymatic Activity of Diacylglycerol Kinase Isozymes in Rat Ovary and Placenta2005

    • Author(s)
      Toya et al.
    • Journal Title

      Cell and Tissure Research (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Adenovirus-mediated overexpression of diacylglycerol kinase-zeta inhibits endothelin-1-induced cardiomyocyte hypertrophy.2005

    • Author(s)
      Takahashi et al.
    • Journal Title

      Circulation 111

      Pages: 1510-1516

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Selective translocation of diacylglycerol kinase zeta in hippocampal neurons under transient forebrain ischemia.2004

    • Author(s)
      Ali et al.
    • Journal Title

      Neuroscience Lettets 372

      Pages: 190-195

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Functional implications of diacylglycerol kinase family.2004

    • Author(s)
      Goto, Kondo
    • Journal Title

      Advance Enzyme Regul 44

      Pages: 187-199

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cloning and characterization of diacylglycerol kinase iota splice variants in rat brain2004

    • Author(s)
      Ito et al.
    • Journal Title

      J. Biol. Chem 279

      Pages: 23317-23326

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Selective translocation of diacylglycerol kinase zeta in hippocampal neurons under transient forebrain ischemia.2004

    • Author(s)
      Ali, H., Nakano, T., Saino-S., S., Hozumi, Y., Katagiri, Y., Kamii, H., Sato, S., Kayama, T., Kondo, H., Goto, K.
    • Journal Title

      Neuroscience Letters 372

      Pages: 190-195

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Functional implications of diacylglycerol kinase family.2004

    • Author(s)
      Goto, K., Kondo, H.
    • Journal Title

      Advance Enzyme Regul. 44

      Pages: 187-199

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cloning and characterization of diacylglycerol kinase iota splice variants in rat brain2004

    • Author(s)
      Ito, T., Hozumi, Y., Saino-S, S., Sakane, R, Kanoh, H., Aoyagi, M., Kondo, H., Goto, K.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 23317-23326

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cloning and characterization of diacylglycerol kinase iota splice variant in rat brain2004

    • Author(s)
      Ito et al.
    • Journal Title

      Journal of Biological Chemistry 279・22

      Pages: 23317-23326

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Selective translocation of diacylglycerol kinase zeta in hippocampal Neurons under transient forebrain ischemia2004

    • Author(s)
      Ali et al.
    • Journal Title

      Neuroscience Letters 372・39

      Pages: 190-195

    • Related Report
      2004 Annual Research Report
  • [Journal Article] An N-terminal fragment of ProSAAS (a Granin-llike neuroendocrine peptide precursor) is associated with tau inclusion in Pick's disease.2003

    • Author(s)
      Kikuchi et al.
    • Journal Title

      Biochem. Biophys. Res. Comm. 308

      Pages: 646-654

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Nuclear localization of diacylglycerol kinase zeta m neurons.2003

    • Author(s)
      Hozumi et al.
    • Journal Title

      Eur. J. Neurosci. 18

      Pages: 1448-1457

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mutant SODl linked to familial amyotrophic lateral sclerosis, but not wild・type SOD1, induced ER stress in COS7 cells and transgenic mice.2003

    • Author(s)
      Tobisawa et al.
    • Journal Title

      Biochem. Biophys. Res. Comm. 303

      Pages: 496-503

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Molecular cloning and characterization of the human diacylglycerol kinase beta gene : alternative splicing generates DGKbeta isotypes with different properties.2003

    • Author(s)
      Caricasole et al.
    • Journal Title

      J. Biol. Chem. 277

      Pages: 4790-4796

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] An N-terminal fragment of ProSAAS (a Granin-like neuroendocrine peptide precursor) is associated with tau inclusion in Pick's disease.2003

    • Author(s)
      Kikuchi, K., Arawaka, S., Koyama, S., Kimura, H., Ren, C.H., Wada, M., Kawanami, T., Kurita, K., Daimon, M., Kawakatsu, S., Kadoya, T., Goto, K., Kato, T.
    • Journal Title

      Biochem.Biophys.Res.Comm. 308

      Pages: 646-654

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Nuclear localization of diacylglycerol kinase zeta in neurons.2003

    • Author(s)
      Hozumi, Y., Ito, T., Nakano, T., Nakagawa, T., Aoyagi, M, Kondo, H., Goto, K.
    • Journal Title

      Eur.J.Neurosci. 18

      Pages: 1448-1457

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mutant SOD1 linked to familial amyotrophic lateral sclerosis, but not wild-type SOD1,induced ER stress in COS7 cells and transgenic mice.2003

    • Author(s)
      Tobisavva, S., Hozumi, Y., Arawaka, S., Koyama.S., Wasa, M., Nagai, M., Aoki, M., Itoyama, Y., Goto, K., Kato, T.
    • Journal Title

      Biochem.Biophys.Res.Comm. 303

      Pages: 496-503

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Molecular cloning and characterization of the human diacylglycerol kinase beta gene : alternative splicing generates DGKbeta isotypes with different properties.2003

    • Author(s)
      Caricasole, A., Bettini, E., Sala, C., Ronearati, R., Kobayasi, N., Caldara, F., Goto, K., Terstappen, G.C.
    • Journal Title

      J.Biol.Chem. 277

      Pages: 4790-4796

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Kikuchi, K., Arawaka, S., Koyama, S., Kimura, H., Ren, C.H., Wada, M., et al.: "An N-terminal fragment of ProSAAS (a Granin-llike neuroendocrine peptide precursor) is associated with tau inclusion in Pick's disease"Biochem.Biophys.Res.Comm.. 308. 646-654 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hozumi, Y., Ito, T., Nakano, T., Nakagawa, T., Aoyagi, M, Kondo, H., Goto, K.: "Nuclear localization of diacylglycerol kinase z in neurons"Eur.J.Neurosci.. 18. 1448-1457 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tobisawa, S., Hozumi, Y., Arawaka, S., Koyama, S., Wasa, M., Nagai, M., et al.: "Mutant SOD1 linked to familial amyotrophic lateral sclerosis, but not wild-type SOD1, induced ER stress in COS7 cells and transgenic mice"Biochem.Biophys.Res.Comm.. 303. 496-503 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Goto, K.: "Subcellular localization and functional implication of diacylglycerol kinase isozymes. In : Nuclear Metabolism and Signalling."Research Signpost, Kerala, India. 16(188) (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Caricasole, A. et al.: "Molecular cloning and characterization of the human diacylglycerol kinase β gene"J. Biol. Chem.. 277. 4790-4796 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 後藤 薫, 近藤尚武: "脳内における脂質性二次メッセンジャー代謝酵素ジアシルグリセロールキナーゼの分子・発現局在の多様性と機能的役割"電子顕微鏡. 37. 183-187 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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